Determination of imipramine and seven of its metabolites in human liver microsomes by a high-performance liquid chromatographic method.
The metabolism of the widely used antidepressant drug imipramine is subject to marked interindividual variation. A sensitive and specific reversed-phase high-performance liquid chromatography method for the simultaneous determination of imipramine and seven of its metabolites in human liver microsomal preparations was developed. These metabolites include 10-hydroxy-desipramine, 10-hydroxyimipramine, 2-hydroxydesipramine, 2-hydroxyimipramine, desipramine, didesmethylimipramine, and imipramine N-oxide. The detection limit for imipramine and the metabolites was approximately 20 pmol. At concentrations of 100 and 500 pmol per tube, the reproducibility showed a coefficient of variation less than 10%, except for the 2-hydroxy-desipramine (16%), 2-hydroxyimipramine (15%), and imipramine N-oxide (17%), all three at 100 pmol per tube. Linear standard curves were obtained for all the compounds within a concentration range of 50 to 1000 pmol per tube. This assay will provide a tool to assess the contribution of different enzymes to the formation of imipramine metabolites.
Zeugin
T B
TB
University of Basel, Department of Pharmacology, Switzerland.
Brosen
K
K
Meyer
U A
UA
D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D007099:Imipramine / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D012015:Reference Standards
D007099:Imipramine